Required Packages and functions

# libraries
library(sas7bdat)
library(sva)
library(reshape)
library(ggplot2)
library(gridExtra)
library(knitr)
library(dplyr)
library(kableExtra)
library(tidyverse)
library(minfi)
library(stringr)
library(limma)
library(IlluminaHumanMethylation450kanno.ilmn12.hg19)
library(minfi)
library(DMRcate)
library(UpSetR)
library(reshape)
library(corrplot)
library(factoextra)
library(ENmix)

# loading annotation
anno = getAnnotation(IlluminaHumanMethylation450kanno.ilmn12.hg19)
anno = data.frame(anno)

# loading functions
setwd('/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local')
source('EWAS functions.R')

Load DNAm and pheno data

load("/Users/annebozack/Box/NIEHS-R01 ONES/Methylation Data/Age7Blood_ComBat_Betas_Mvals_filteredProbes_metalAnalaysis.RData")

dim(pDatAge7Metal)
# 333 164

dim(ComBat.Mvalues.Metals)
# 394460    333

rownames(pDatAge7Metal) = pDatAge7Metal$samplename

EWAS

As

DMP_As = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'As_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  23361 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  16750 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.933939 
 
# Number of DMRs identified:   6 

# rm(DMP_As); gc()

DMRs

chr start end p length fdr sidak nprobe
2 113992761 113993313 0.00e+00 552 0.00e+00 0.0000000 8
3 46759437 46759698 0.00e+00 261 0.00e+00 0.0000003 7
1 228395659 228396009 0.00e+00 350 0.00e+00 0.0000007 5
17 1395863 1396123 0.00e+00 260 0.00e+00 0.0000018 5
17 16593581 16593613 1.00e-07 32 1.00e-07 0.0007180 4
17 75315562 75315667 4.63e-05 105 4.63e-05 0.1596525 3

No adjustment for fish consumption

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As/As_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As/As_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As/As_log2_manhattan_DMP_adj.png")

As, female

pDatAge7Metal_F = pDatAge7Metal[pDatAge7Metal$female_d == 1,]
pDatAge7Metal_F$race_child2 = as.factor(as.numeric(pDatAge7Metal_F$race_child2))

DMP_As_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'As_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  26064 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  15925 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.9033443 
 
# Number of DMRs identified:   4 

rm(DMP_As_F); gc()

DMRs

chr start end p length fdr sidak nprobe
1 11561496 11561711 0.0e+00 215 0.0e+00 0.0000022 3
2 113992761 113993142 0.0e+00 381 0.0e+00 0.0000018 6
7 76027000 76027101 0.0e+00 101 0.0e+00 0.0000119 3
2 198651075 198651347 6.3e-06 272 6.3e-06 0.0090701 3

No adjustment for fish consumption

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_F/As_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_F/As_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_F/As_log2_manhattan_DMP_adj.png")

As, male

pDatAge7Metal_M = pDatAge7Metal[pDatAge7Metal$female_d == 0,]
pDatAge7Metal_M$race_child2 = as.factor(as.numeric(pDatAge7Metal_M$race_child2))

DMP_As_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'As_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  11497 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  14521 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8501198 
 
# Number of DMRs identified:   3 

# rm(DMP_As_M); gc()

DMRs

chr start end p length fdr sidak nprobe
17 47091977 47092178 0 201 0 1.2e-06 4
2 164204627 164205032 0 405 0 5.2e-06 5
5 6755149 6755439 0 290 0 2.1e-05 5

No adjustment for fish consumption

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_M/As_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_M/As_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/As_M/As_log2_manhattan_DMP_adj.png")

Ba

DMP_Ba = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Ba_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  11801 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  11923 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.7860875 
 
# Number of DMRs identified:   3 

rm(DMP_Ba); gc()

DMRs

chr start end p length fdr sidak nprobe
17 6899084 6899577 0.000000 493 0.000000 0.0000000 10
16 1583809 1584118 0.000000 309 0.000000 0.0000083 6
6 32145551 32145654 0.000806 103 0.000806 0.9544043 5
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba/Ba_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba/Ba_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba/Ba_log2_manhattan_DMP_adj.png")

Ba, female

DMP_Ba_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Ba_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  29651 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  23451 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.216079 

rm(DMP_Ba_F); gc()

DMRs

chr start end p length fdr sidak nprobe
17 6899084 6899577 0.0000000 493 0.0000000 0.0000000 10
17 37123637 37123949 0.0000000 312 0.0000000 0.0000068 9
2 183943387 183943551 0.0000000 164 0.0000000 0.0000317 5
3 112359487 112359652 0.0000001 165 0.0000001 0.0001519 6
7 94285269 94285329 0.0000446 60 0.0000536 0.2543856 5
1 234367321 234367443 0.0002131 122 0.0002131 0.4978958 2
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_F/Ba_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_F/Ba_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_F/Ba_log2_manhattan_DMP_adj.png")

Ba, male

DMP_Ba_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Ba_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  25363 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  28150 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.261352 

rm(DMP_Ba_M); gc()

DMRs

chr start end p length fdr sidak nprobe
16 1583809 1584118 0e+00 309 0e+00 0.00e+00 6
19 50194119 50194252 0e+00 133 0e+00 2.30e-06 5
6 29595001 29595335 1e-07 334 1e-07 9.07e-05 8
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_M/Ba_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_M/Ba_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Ba_M/Ba_log2_manhattan_DMP_adj.png")

Cd

DMP_Cd = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Cd_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  9428 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  11922 
# Adjusted, FDR<0.05:  1 
# Adjusted, pBonf<0.05:  1 
# Adjusted, lambda:  0.8236619 

rm(DMP_Cd); gc()

FDR-significant DMPs

logFC_CI AveExpr P.Value adj.P.Val adj.P.Val.bonf chr pos gene
cg07044523 0.26 (0.17 ,0.34) 5.28 0 0.0017741 0.0018 chr1 153514376 S100A5

DMRs

chr start end p length fdr sidak nprobe
7 158045979 158046166 0.0000000 187 0.0000000 6.10e-06 3
5 23507449 23507656 0.0000000 207 0.0000000 1.43e-05 5
17 46685291 46685448 0.0000000 157 0.0000000 8.55e-05 5
7 27184158 27184188 0.0024888 30 0.0024888 1.00e+00 4
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd/Cd_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd/Cd_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd/Cd_log2_manhattan_DMP_adj.png")

Cd, female

DMP_Cd_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Cd_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  13276 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  13294 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8195885 
 
# Number of DMRs identified:   7 

# rm(DMP_Cd_F); gc()

DMRs

chr start end p length fdr sidak nprobe
6 32164926 32165321 0.0000000 395 0.0000000 0.0000000 7
17 46685291 46685448 0.0000000 157 0.0000000 0.0000003 5
6 1624385 1624442 0.0000000 57 0.0000001 0.0002031 2
5 23507449 23507656 0.0000001 207 0.0000001 0.0000961 5
6 88757301 88757392 0.0000001 91 0.0000001 0.0002665 5
11 73357094 73357276 0.0000030 182 0.0000035 0.0064276 6
5 132113754 132113860 0.0158178 106 0.0158178 1.0000000 3
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_F/Cd_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_F/Cd_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_F/Cd_log2_manhattan_DMP_adj.png")

Cd, male

DMP_Cd_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Cd_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  16666 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  19823 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.072079 

# Number of DMRs identified:   3 

# rm(DMP_Cd_M); gc()

DMRs

chr start end p length fdr sidak nprobe
20 61446961 61447369 0.00e+00 408 0.00e+00 0.0000000 11
7 50518572 50518647 1.80e-06 75 2.70e-06 0.0093850 2
6 28446839 28447087 6.55e-05 248 6.55e-05 0.0989943 2
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_M/Cd_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_M/Cd_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cd_M/Cd_log2_manhattan_DMP_adj.png")

Cr

DMP_Cr = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Cr_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  29723 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  23245 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.099732 
 
# Number of identified DMR:  0

rm(DMP_Cr); gc()

DMRs

chr start end p length fdr sidak nprobe
NA NA NA NA NA NA NA NA

No adjustment for fish consumption

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr/Cr_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr/Cr_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr/Cr_log2_manhattan_DMP_adj.png")

Cr, female

DMP_Cr_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Cr_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  26701 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  25616 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.219568 
 
# Number of identified DMR:  0

rm(DMP_Cr_F); gc()

DMRs

chr start end p length fdr sidak nprobe
NA NA NA NA NA NA NA NA
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_F/Cr_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_F/Cr_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_F/Cr_log2_manhattan_DMP_adj.png")

Cr, male

DMP_Cr_M = run_wEWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Cr_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  17887 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  12418 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8679592 

# Number of DMRs identified:   1 

rm(DMP_Cr_M); gc()

DMRs

chr start end p length fdr sidak nprobe
17 46685291 46685448 0 157 0 1.05e-05 5
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_M/Cr_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_M/Cr_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cr_M/Cr_log2_manhattan_DMP_adj.png")

Cs

DMP_Cs = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Cs_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  16687 
# Unadjusted, FDR<0.05:  4 
# Unadjusted, pBonf<0.05:  2 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  13314 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8363101 
 
# Number of DMRs identified:   4 

rm(DMP_Cs); gc()

DMRs

chr start end p length fdr sidak nprobe
6 32847526 32847845 0.0000000 319 0.0000000 2.50e-06 16
6 33280051 33280228 0.0000000 177 0.0000001 6.02e-05 6
13 47472137 47472429 0.0000000 292 0.0000001 5.48e-05 10
20 57427729 57427762 0.0124658 33 0.0124658 1.00e+00 3
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs/Cs_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs/Cs_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs/Cs_log2_manhattan_DMP_adj.png")

Cs, female

DMP_Cs_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Cs_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  25871 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  15950 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.9510468 
 
# Number of DMRs identified:   4 

rm(DMP_Cs_F); gc()

DMRs

chr start end p length fdr sidak nprobe
1 200272111 200272215 0 104 0 5.70e-06 3
6 29648378 29648628 0 250 0 2.89e-05 8
20 3145355 3145597 0 242 0 3.76e-05 3
5 78985424 78985592 0 168 0 9.92e-05 9
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_F/Cs_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_F/Cs_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_F/Cs_log2_manhattan_DMP_adj.png")

Cs, male

DMP_Cs_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Cs_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  15896 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  14066 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8664272 
 
# rm(DMP_Cs_M); gc()

DMRs

chr start end p length fdr sidak nprobe
20 57427442 57427973 0 531 0 0 17
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_M/Cs_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_M/Cs_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cs_M/Cs_log2_manhattan_DMP_adj.png")

Cu

DMP_Cu = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Cu_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  10199 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  19919 
# Adjusted, FDR<0.05:  29 
# Adjusted, pBonf<0.05:  7 
# Adjusted, lambda:  1.081857 
 
# Number of DMRs identified:   18 

# rm(DMP_Cu); gc()

FDR-significant DMPs

logFC_CI AveExpr P.Value adj.P.Val adj.P.Val.bonf chr pos gene
cg00082497 -0.25 (-0.36 ,-0.15) -5.32 2.6e-06 0.0361295 1.0000 chr1 32802133 MARCKSL1
cg00116766 0.42 (0.28 ,0.56) 2.04 0.0e+00 0.0010722 0.0018 chr16 9857614 GRIN2A;GRIN2A;GRIN2A
cg00908120 0.51 (0.33 ,0.7) 6.26 1.0e-07 0.0063015 0.0567 chr16 72872925 ZFHX3;ZFHX3
cg02155957 0.38 (0.23 ,0.52) 3.25 6.0e-07 0.0142130 0.2558 chr1 46930731
cg04015129 0.7 (0.44 ,0.96) 4.28 3.0e-07 0.0085878 0.1031 chr10 1058036 GTPBP4
cg04692924 -0.42 (-0.59 ,-0.26) -6.61 1.0e-06 0.0183556 0.3855 chr1 161720042 DUSP12
cg05051957 -0.45 (-0.63 ,-0.28) -5.60 4.0e-07 0.0108039 0.1621 chr8 141522459 CHRAC1;CHRAC1
cg05955013 -0.39 (-0.54 ,-0.24) -6.28 5.0e-07 0.0111376 0.1782 chr17 45056646 RPRML
cg06723863 -0.26 (-0.36 ,-0.15) -5.98 1.8e-06 0.0289638 0.6994 chr16 68270129 ESRP2;ESRP2
cg07380021 -0.5 (-0.69 ,-0.32) -5.42 1.0e-07 0.0063015 0.0541 chr1 206755252 RASSF5;RASSF5;RASSF5
cg07831553 0.6 (0.36 ,0.85) 3.37 2.7e-06 0.0361295 1.0000 chr19 48796974
cg08370347 0.51 (0.3 ,0.71) 3.91 1.9e-06 0.0289638 0.7331 chr5 171571793 STK10
cg10145926 0.61 (0.38 ,0.83) 5.31 2.0e-07 0.0073929 0.0813 chr14 95875792 C14orf139
cg10653573 0.82 (0.49 ,1.15) 5.43 1.4e-06 0.0244817 0.5386 chr8 141347297 TRAPPC9;TRAPPC9
cg10923018 0.24 (0.16 ,0.32) 2.75 0.0e+00 0.0028603 0.0145 chr6 31743769 C6orf27
cg11608893 0.61 (0.36 ,0.85) 6.05 1.9e-06 0.0289638 0.7596 chr6 32059542 TNXB
cg12067421 -0.47 (-0.62 ,-0.31) 2.01 0.0e+00 0.0010722 0.0032 chr1 203246482
cg13434714 -0.42 (-0.58 ,-0.26) -5.77 8.0e-07 0.0168736 0.3206 chr12 6936787 LEPREL2
cg15790767 1.04 (0.66 ,1.42) 3.84 1.0e-07 0.0063015 0.0455 chr6 13431216 GFOD1
cg17143270 0.83 (0.52 ,1.14) 5.74 3.0e-07 0.0093778 0.1313 chr1 91532819
cg18299835 -0.23 (-0.33 ,-0.14) -4.13 2.0e-06 0.0289638 0.7820 chr19 13207445 NFIX
cg18714712 -0.54 (-0.72 ,-0.36) -5.97 0.0e+00 0.0010722 0.0030 chr19 49866917 DKKL1;TEAD2
cg19532212 0.49 (0.3 ,0.67) 4.46 3.0e-07 0.0087176 0.1133 chr17 56769430 TEX14;RAD51C;TEX14;RAD51C
cg19842134 -0.29 (-0.4 ,-0.17) -3.53 9.0e-07 0.0170970 0.3419 chr12 54070591 ATP5G2;ATP5G2
cg20365618 -0.24 (-0.34 ,-0.15) 0.42 1.4e-06 0.0245000 0.5635 chr10 121578384 INPP5F;INPP5F
cg23477849 0.28 (0.19 ,0.38) 4.88 0.0e+00 0.0023982 0.0096 chr19 5698492 LONP1
cg25954729 -0.22 (-0.3 ,-0.14) -6.34 2.0e-07 0.0064642 0.0646 chr11 66610784 RCE1;C11orf80;RCE1
cg26708724 0.66 (0.41 ,0.91) 6.73 5.0e-07 0.0123375 0.2097 chr4 187509785 FAT1
cg27565067 0.48 (0.31 ,0.65) 6.20 0.0e+00 0.0028603 0.0172 chr17 149484 RPH3AL

DMRs

chr start end p length fdr sidak nprobe
22 45704901 45705265 0.0e+00 364 0.0e+00 0.0000000 7
20 35169538 35169886 0.0e+00 348 0.0e+00 0.0000000 6
16 66304366 66304585 0.0e+00 219 0.0e+00 0.0000001 3
10 121578136 121578639 0.0e+00 503 0.0e+00 0.0000001 4
12 54070516 54070610 0.0e+00 94 0.0e+00 0.0000007 5
16 8806530 8806756 0.0e+00 226 0.0e+00 0.0000004 7
17 149483 149488 0.0e+00 5 0.0e+00 0.0001511 2
6 1604012 1604212 0.0e+00 200 0.0e+00 0.0000158 5
20 3052114 3052483 0.0e+00 369 0.0e+00 0.0000229 9
17 1395863 1396123 0.0e+00 260 0.0e+00 0.0000413 5
19 55660590 55660625 0.0e+00 35 0.0e+00 0.0003111 4
2 130345204 130345405 1.0e-07 201 1.0e-07 0.0001057 3
15 100048370 100048500 1.0e-07 130 1.0e-07 0.0001709 3
17 47091977 47092178 1.0e-07 201 1.0e-07 0.0001289 4
19 50194119 50194252 1.0e-07 133 1.0e-07 0.0002880 5
13 100310161 100310405 1.0e-07 244 1.0e-07 0.0001625 4
11 19736149 19736333 1.0e-07 184 1.0e-07 0.0002511 5
1 207082827 207082900 1.3e-06 73 1.3e-06 0.0067921 2
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu/Cu_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu/Cu_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu/Cu_log2_manhattan_DMP_adj.png")

Cu, female

DMP_Cu_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Cu_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  19233 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  16219 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.9599566 
 
# Number of DMRs identified:   11 
   # chr     start       end            p length          fdr        sidak nprobe
# 1    5    191295    191806 2.084698e-12    511 2.293168e-11 1.609231e-09      9
# 2    6  32063990  32064810 4.914157e-12    820 2.702787e-11 2.363960e-09     30
# 3   15  81426346  81426610 1.166735e-10    264 4.278029e-10 1.743297e-07      7
# 4   11  73357094  73357396 3.201810e-08    302 8.804977e-08 4.181985e-05      7
# 5    2  74875226  74875536 5.410336e-08    310 1.190274e-07 6.884154e-05      7
# 6   21  37442288  37442476 1.402076e-07    188 2.309027e-07 2.941391e-04      3
# 7    1 120174148 120174361 1.507576e-07    213 2.309027e-07 2.791527e-04      2
# 8   17   1395863   1396123 1.679292e-07    260 2.309027e-07 2.547420e-04      5
# 9    8  95962351  95962383 2.534889e-06     32 3.098197e-06 3.076414e-02      4
# 10   6  31734191  31734401 3.970020e-05    210 4.367022e-05 7.186081e-02      6
# 11  19  23941312  23941438 1.175697e-04    126 1.175697e-04 3.079446e-01      3

# rm(DMP_Cu_F); gc()

DMRs

chr start end p length fdr sidak nprobe
5 191295 191806 0.0000000 511 0.0000000 0.0000000 9
6 32063990 32064810 0.0000000 820 0.0000000 0.0000000 30
15 81426346 81426610 0.0000000 264 0.0000000 0.0000002 7
11 73357094 73357396 0.0000000 302 0.0000001 0.0000418 7
2 74875226 74875536 0.0000001 310 0.0000001 0.0000688 7
21 37442288 37442476 0.0000001 188 0.0000002 0.0002941 3
1 120174148 120174361 0.0000002 213 0.0000002 0.0002792 2
17 1395863 1396123 0.0000002 260 0.0000002 0.0002547 5
8 95962351 95962383 0.0000025 32 0.0000031 0.0307641 4
6 31734191 31734401 0.0000397 210 0.0000437 0.0718608 6
19 23941312 23941438 0.0001176 126 0.0001176 0.3079446 3
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_F/Cu_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_F/Cu_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_F/Cu_log2_manhattan_DMP_adj.png")

Cu, male

DMP_Cu_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Cu_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  8255 
# Unadjusted, FDR<0.05:  32 
# Unadjusted, pBonf<0.05:  5 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  12165 
# Adjusted, FDR<0.05:  46 
# Adjusted, pBonf<0.05:  13 
# Adjusted, lambda:  0.7385324 

# Number of DMRs identified:   13 

# rm(DMP_Cu_M); gc()

FDR-significant DMPs

logFC_CI AveExpr P.Value adj.P.Val adj.P.Val.bonf chr pos gene
cg00908120 0.7 (0.45 ,0.95) 6.29 1.0e-07 0.0036055 0.0505 chr16 72872925 ZFHX3;ZFHX3
cg01007589 0.93 (0.61 ,1.26) 4.79 1.0e-07 0.0024477 0.0282 chr19 49894178 CCDC155
cg01063965 -0.27 (-0.38 ,-0.17) -6.44 3.0e-07 0.0080101 0.1323 chr11 695461 TMEM80;TMEM80;DEAF1;DEAF1
cg01447660 0.38 (0.22 ,0.53) -0.92 4.3e-06 0.0399576 1.0000 chr2 69152678
cg01485439 0.5 (0.31 ,0.69) 3.65 8.0e-07 0.0143550 0.3169 chr11 67225937 CABP4
cg02155957 0.48 (0.29 ,0.67) 3.22 1.6e-06 0.0203703 0.6165 chr1 46930731
cg02196294 -0.26 (-0.37 ,-0.15) -5.41 5.0e-06 0.0450418 1.0000 chr6 39197260 KCNK5
cg02490920 0.37 (0.23 ,0.51) 1.34 4.0e-07 0.0080101 0.1437 chr3 50304406 SEMA3B;SEMA3B
cg02968175 0.31 (0.19 ,0.42) 5.76 4.0e-07 0.0080101 0.1386 chr16 4690020 MGRN1;MGRN1;MGRN1;MGRN1
cg03717239 0.3 (0.18 ,0.42) 0.51 2.6e-06 0.0277414 1.0000 chr8 145574318
cg04015129 0.84 (0.56 ,1.13) 4.27 0.0e+00 0.0010730 0.0097 chr10 1058036 GTPBP4
cg04406071 -0.3 (-0.41 ,-0.19) -6.07 4.0e-07 0.0080101 0.1442 chr17 59489784 C17orf82
cg04692924 -0.6 (-0.83 ,-0.36) -6.58 1.1e-06 0.0160189 0.4165 chr1 161720042 DUSP12
cg05051957 -0.61 (-0.85 ,-0.37) -5.61 1.7e-06 0.0203703 0.6518 chr8 141522459 CHRAC1;CHRAC1
cg05955013 -0.48 (-0.67 ,-0.29) -6.30 2.1e-06 0.0238012 0.8092 chr17 45056646 RPRML
cg07380021 -0.68 (-0.9 ,-0.46) -5.43 0.0e+00 0.0008408 0.0025 chr1 206755252 RASSF5;RASSF5;RASSF5
cg08329655 -0.43 (-0.6 ,-0.26) -5.88 1.2e-06 0.0169324 0.4680 chr11 7534677 PPFIBP2
cg08459368 0.59 (0.36 ,0.82) 2.70 1.0e-06 0.0160189 0.4117 chr11 61974948 SCGB2A1
cg08760128 0.31 (0.19 ,0.43) 6.73 8.0e-07 0.0143550 0.3302 chr16 4723507 MGRN1;MGRN1;MGRN1;MGRN1
cg10053073 -0.21 (-0.31 ,-0.12) 0.54 5.5e-06 0.0484367 1.0000 chr17 73623182 RECQL5
cg10266648 1.04 (0.68 ,1.41) 5.98 1.0e-07 0.0024477 0.0318 chr2 106560529
cg10923018 0.35 (0.24 ,0.47) 2.73 0.0e+00 0.0006035 0.0012 chr6 31743769 C6orf27
cg11608893 0.95 (0.64 ,1.26) 6.08 0.0e+00 0.0008871 0.0040 chr6 32059542 TNXB
cg12243007 0.45 (0.26 ,0.64) -0.77 4.5e-06 0.0409168 1.0000 chr17 184018 RPH3AL
cg13434714 -0.67 (-0.86 ,-0.47) -5.78 0.0e+00 0.0001002 0.0001 chr12 6936787 LEPREL2
cg13989834 0.54 (0.33 ,0.75) 3.14 1.3e-06 0.0181143 0.5253 chr9 134400392 UCK1;UCK1
cg15389183 -0.22 (-0.31 ,-0.13) -6.19 2.3e-06 0.0264805 0.9268 chr14 102829482 TECPR2;CINP
cg15790767 1.18 (0.69 ,1.66) 3.86 3.8e-06 0.0370497 1.0000 chr6 13431216 GFOD1
cg16068812 -1.01 (-1.42 ,-0.61) -4.27 2.0e-06 0.0238012 0.8051 chr21 44528396 U2AF1;U2AF1;U2AF1
cg16496814 0.28 (0.17 ,0.39) 5.22 1.2e-06 0.0169324 0.4741 chr11 9778721
cg16656826 0.33 (0.2 ,0.45) 0.14 6.0e-07 0.0126948 0.2539 chr5 159343871 ADRA1B;ADRA1B
cg18670846 0.73 (0.43 ,1.03) -2.30 3.9e-06 0.0378865 1.0000 chr2 68917482
cg18714712 -0.73 (-0.97 ,-0.48) -5.95 0.0e+00 0.0010211 0.0082 chr19 49866917 DKKL1;TEAD2
cg19005275 0.68 (0.45 ,0.92) 4.29 0.0e+00 0.0016338 0.0163 chr12 113588263 CCDC42B
cg19532212 0.7 (0.44 ,0.96) 4.42 4.0e-07 0.0080757 0.1534 chr17 56769430 TEX14;RAD51C;TEX14;RAD51C
cg20365618 -0.35 (-0.46 ,-0.23) 0.40 0.0e+00 0.0010211 0.0081 chr10 121578384 INPP5F;INPP5F
cg21373263 0.79 (0.49 ,1.1) 3.29 7.0e-07 0.0137845 0.2895 chr10 126751982 CTBP2;CTBP2
cg21864868 0.66 (0.4 ,0.92) 4.22 9.0e-07 0.0153134 0.3675 chr17 46673002 LOC404266;LOC404266;LOC404266;LOC404266;LOC404266
cg22240394 1.04 (0.62 ,1.46) 6.82 2.6e-06 0.0277414 1.0000 chr3 186211630
cg22286640 -0.78 (-1.1 ,-0.46) -4.65 3.6e-06 0.0363886 1.0000 chr8 67026828
cg23312431 0.34 (0.2 ,0.47) -0.37 1.6e-06 0.0203703 0.6357 chr21 45773997 TRPM2
cg23477849 0.39 (0.25 ,0.52) 4.90 1.0e-07 0.0024477 0.0312 chr19 5698492 LONP1
cg24543538 0.83 (0.49 ,1.16) 3.22 2.7e-06 0.0281802 1.0000 chr2 241569846 GPR35
cg25954729 -0.31 (-0.41 ,-0.2) -6.37 0.0e+00 0.0010211 0.0064 chr11 66610784 RCE1;C11orf80;RCE1
cg26708724 0.97 (0.65 ,1.28) 6.72 0.0e+00 0.0008871 0.0044 chr4 187509785 FAT1
cg27503275 0.43 (0.25 ,0.61) 4.12 5.7e-06 0.0487795 1.0000 chr6 3880016

DMRs

chr start end p length fdr sidak nprobe
10 121578136 121578846 0.0000000 710 0.0000000 0.0000000 5
22 45704901 45705265 0.0000000 364 0.0000000 0.0000000 7
21 45773781 45773997 0.0000000 216 0.0000000 0.0000008 2
4 24796918 24797176 0.0000000 258 0.0000000 0.0000028 6
19 50194119 50194252 0.0000000 133 0.0000000 0.0000115 5
17 70723226 70723386 0.0000000 160 0.0000000 0.0000390 2
20 35169593 35169886 0.0000000 293 0.0000000 0.0000228 5
3 16216093 16216215 0.0000000 122 0.0000001 0.0001340 4
14 78447480 78447640 0.0000000 160 0.0000001 0.0001027 3
17 78549323 78549371 0.0000001 48 0.0000001 0.0005317 3
17 149483 149488 0.0000001 5 0.0000001 0.0062718 2
12 54070516 54070591 0.0000102 75 0.0000110 0.0521028 4
16 8806752 8806756 0.0028704 4 0.0028704 1.0000000 2
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_M/Cu_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_M/Cu_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Cu_M/Cu_log2_manhattan_DMP_adj.png")

Hg

DMP_Hg = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Hg_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg')

# Unadjusted, N =  326 
# Unadjusted, p<0.05:  37293 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  326 
# Adjusted, p<0.05:  28324 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.24761 
 
# Number of DMRs identified:   4 

# rm(DMP_Hg); gc()

DMRs

chr start end p length fdr sidak nprobe
17 46681110 46681401 0.0000000 291 0.0000000 0.0000012 6
6 31846768 31847009 0.0000000 241 0.0000000 0.0000145 9
10 131843516 131843725 0.0000023 209 0.0000031 0.0043852 3
3 42977952 42978026 0.0004605 74 0.0004605 0.9141599 2
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg/Hg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg/Hg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg/Hg_log2_manhattan_DMP_adj.png")

Hg, female

DMP_Hg_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Hg_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_F')

# Unadjusted, N =  154 
# Unadjusted, p<0.05:  35686 
# Unadjusted, FDR<0.05:  156 
# Unadjusted, pBonf<0.05:  1 
 
# Adjusted, N =  154 
# Adjusted, p<0.05:  15125 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8835584 

# Number of DMRs identified:   3 

# rm(DMP_Hg_F); gc()

DMRs

chr start end p length fdr sidak nprobe
12 47219625 47220092 0 467 0 0.00e+00 12
4 165877874 165878136 0 262 0 3.10e-06 6
7 27143234 27143478 0 244 0 4.58e-05 7
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_F/Hg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_F/Hg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_F/Hg_log2_manhattan_DMP_adj.png")

Hg, male

DMP_Hg_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Hg_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_M')

# Unadjusted, N =  172 
# Unadjusted, p<0.05:  22412 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  172 
# Adjusted, p<0.05:  26536 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.269744 
 
# Number of DMRs identified:   10 

# rm(DMP_Hg_M); gc()

DMRs

chr start end p length fdr sidak nprobe
6 31846768 31847009 0.0000000 241 0.0000000 0.0000000 9
11 18477152 18477680 0.0000000 528 0.0000000 0.0000000 8
11 18433499 18433887 0.0000000 388 0.0000000 0.0000000 5
5 502290 502571 0.0000000 281 0.0000000 0.0000009 3
6 33282735 33283162 0.0000000 427 0.0000000 0.0000020 20
14 104690039 104690244 0.0000000 205 0.0000000 0.0000089 5
1 147737015 147737207 0.0000001 192 0.0000002 0.0003078 4
1 2345151 2345410 0.0000002 259 0.0000002 0.0002524 8
1 117317981 117318133 0.0009779 152 0.0010866 0.9210590 2
11 368613 368683 0.0015854 70 0.0015854 0.9998691 3
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_M/Hg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_M/Hg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Hg_M/Hg_log2_manhattan_DMP_adj.png")

Mg

DMP_Mg = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Mg_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  18232 
# Unadjusted, FDR<0.05:  1 
# Unadjusted, pBonf<0.05:  1 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  15760 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8766869 
 
# Number of DMRs identified:   4 

# rm(DMP_Mg); gc()

DMRs

chr start end p length fdr sidak nprobe
20 3051953 3052483 0.0e+00 530 0.0e+00 0.0000000 10
2 240196768 240196996 0.0e+00 228 1.0e-07 0.0000647 3
6 31543539 31543686 0.0e+00 147 1.0e-07 0.0001052 8
11 368564 368712 1.6e-06 148 1.6e-06 0.0043050 7
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg/Mg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg/Mg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg/Mg_log2_manhattan_DMP_adj.png")

Mg, female

DMP_Mg_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Mg_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  33977 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  20218 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  1.061758 
 
# Number of DMRs identified:   1 

# rm(DMP_Mg_F); gc()

DMRs

chr start end p length fdr sidak nprobe
6 10884093 10884140 0.0002934 47 0.0002934 0.9147992 2
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_F/Mg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_F/Mg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_F/Mg_log2_manhattan_DMP_adj.png")

Mg, male

DMP_Mg_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Mg_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  9395 
# Unadjusted, FDR<0.05:  7 
# Unadjusted, pBonf<0.05:  5 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  12911 
# Adjusted, FDR<0.05:  3 
# Adjusted, pBonf<0.05:  3 
# Adjusted, lambda:  0.7788244 
 
# Number of DMRs identified:   3 

# rm(DMP_Mg_M); gc()

FDR-significant DMPs

logFC_CI AveExpr P.Value adj.P.Val adj.P.Val.bonf chr pos gene
cg13434714 -0.59 (-0.78 ,-0.41) -5.78 0e+00 0.0016685 0.0017 chr12 6936787 LEPREL2
cg18670846 0.83 (0.55 ,1.1) -2.30 0e+00 0.0035334 0.0071 chr2 68917482
cg26708724 0.88 (0.57 ,1.18) 6.72 1e-07 0.0073831 0.0221 chr4 187509785 FAT1

DMRs

chr start end p length fdr sidak nprobe
2 152830504 152830665 0 161 0 4.49e-05 5
17 37123668 37123949 0 281 0 4.39e-05 8
5 23507449 23507656 0 207 0 9.40e-05 5
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_M/Mg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_M/Mg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mg_M/Mg_log2_manhattan_DMP_adj.png")

Mn

DMP_Mn = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Mn_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  27983 
# Unadjusted, FDR<0.05:  6 
# Unadjusted, pBonf<0.05:  1 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  39522 
# Adjusted, FDR<0.05:  13 
# Adjusted, pBonf<0.05:  3 
# Adjusted, lambda:  1.362045 

# Number of DMRs identified:   8 

# rm(DMP_Mn); gc()

FDR-significant DMPs

logFC_CI AveExpr P.Value adj.P.Val adj.P.Val.bonf chr pos gene
cg00808511 0.18 (0.11 ,0.25) 2.86 1.6e-06 0.0495452 0.6441 chr16 52495237 TOX3;TOX3
cg03716590 0.18 (0.11 ,0.25) 5.09 8.0e-07 0.0324264 0.3243 chr7 95435309 DYNC1I1;DYNC1I1;DYNC1I1
cg05613017 0.2 (0.12 ,0.28) 5.33 5.0e-07 0.0226928 0.2042 chr12 65589446 LEMD3;LEMD3
cg09856068 -0.11 (-0.16 ,-0.07) -4.37 5.0e-07 0.0226928 0.1878 chr5 170878246 FGF18
cg11063328 -0.16 (-0.22 ,-0.1) -6.02 4.0e-07 0.0226928 0.1593 chr11 18343203 GTF2H1;HPS5;HPS5;HPS5;GTF2H1
cg13834844 -0.1 (-0.14 ,-0.06) -5.14 1.0e-07 0.0140080 0.0560 chr10 102415320
cg14252211 0.19 (0.13 ,0.26) 5.85 0.0e+00 0.0030032 0.0060 chr1 25919394
cg19407717 0.31 (0.22 ,0.4) 4.03 0.0e+00 0.0000228 0.0000 chr2 1544120 TPO;TPO;TPO;TPO
cg19425870 -0.15 (-0.21 ,-0.09) -6.46 1.0e-06 0.0366926 0.4036 chr11 3876808 STIM1
cg22586726 0.27 (0.16 ,0.38) -0.97 1.5e-06 0.0495452 0.6014 chr10 134150542 LRRC27;LRRC27;LRRC27;LRRC27;LRRC27
cg24196240 0.33 (0.21 ,0.45) 5.25 1.0e-07 0.0119610 0.0359 chr21 36096009 NCRNA00160
cg25101184 0.25 (0.15 ,0.34) 3.38 4.0e-07 0.0226928 0.1753 chr14 56231604 RPL13AP3
cg27095984 -0.19 (-0.26 ,-0.12) 5.27 3.0e-07 0.0224715 0.1124 chr13 21652115

DMRs

chr start end p length fdr sidak nprobe
10 134150488 134150760 0.0000000 272 0.0000000 0.0000000 7
19 21657528 21657756 0.0000000 228 0.0000000 0.0000001 4
16 30572738 30573013 0.0000000 275 0.0000000 0.0000014 5
10 45406680 45406847 0.0000000 167 0.0000000 0.0000580 3
16 73100425 73100510 0.0000000 85 0.0000001 0.0001462 2
20 61659979 61660250 0.0000001 271 0.0000001 0.0000854 2
10 35484767 35484824 0.0001922 57 0.0002197 0.7356060 3
15 91473290 91473365 0.0005497 75 0.0005497 0.9445390 2
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn/Mn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn/Mn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn/Mn_log2_manhattan_DMP_adj.png")

Mn, female

DMP_Mn_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Mn_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  28256 
# Unadjusted, FDR<0.05:  3 
# Unadjusted, pBonf<0.05:  3 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  39254 
# Adjusted, FDR<0.05:  3 
# Adjusted, pBonf<0.05:  2 
# Adjusted, lambda:  1.350311 

# Number of DMRs identified:   3 

# rm(DMP_Mn_F); gc()

FDR-significant DMPs

logFC_CI AveExpr P.Value adj.P.Val adj.P.Val.bonf chr pos gene
cg11063328 -0.25 (-0.33 ,-0.17) -6.00 0e+00 0.0008720 0.0009 chr11 18343203 GTF2H1;HPS5;HPS5;HPS5;GTF2H1
cg19425870 -0.24 (-0.31 ,-0.16) -6.45 0e+00 0.0011946 0.0024 chr11 3876808 STIM1
cg22396353 -0.15 (-0.2 ,-0.09) -6.10 2e-07 0.0207498 0.0622 chr22 46692687 GTSE1;GTSE1;CN5H6.4

DMRs

chr start end p length fdr sidak nprobe
16 73100425 73100510 0.0e+00 85 1.0e-07 0.0001673 2
6 3849410 3849690 5.0e-07 280 7.0e-07 0.0006411 10
11 76839190 76839217 4.6e-06 27 4.6e-06 0.0654209 3
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_F/Mn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_F/Mn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_F/Mn_log2_manhattan_DMP_adj.png")

Mn, male

DMP_Mn_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Mn_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  14905 
# Unadjusted, FDR<0.05:  27 
# Unadjusted, pBonf<0.05:  9 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  19332 
# Adjusted, FDR<0.05:  32 
# Adjusted, pBonf<0.05:  15 
# Adjusted, lambda:  0.9962195 
# Number of DMRs identified:   12 

rm(DMP_Mn_M); gc()
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_M/Mn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_M/Mn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Mn_M/Mn_log2_manhattan_DMP_adj.png")

FDR-significant DMPs

logFC_CI AveExpr P.Value adj.P.Val adj.P.Val.bonf chr pos gene
cg03425412 -0.23 (-0.31 ,-0.14) -5.94 7.0e-07 0.0133241 0.2798 chr20 21500337
cg04143120 0.42 (0.28 ,0.55) 6.79 0.0e+00 0.0007642 0.0053 chr11 72968848
cg04885068 0.19 (0.12 ,0.26) 6.47 1.0e-07 0.0024926 0.0306 chr1 9099298 SLC2A5;SLC2A5
cg05041382 -0.12 (-0.17 ,-0.07) -6.39 2.0e-06 0.0288229 0.7782 chr13 50366546 KPNA3
cg05249026 -0.17 (-0.23 ,-0.11) -2.36 2.0e-07 0.0045702 0.0777 chr16 11031524 DEXI
cg06051716 0.35 (0.24 ,0.46) 6.49 0.0e+00 0.0003949 0.0024 chr6 169225783
cg06184647 -0.14 (-0.2 ,-0.08) -5.92 3.7e-06 0.0455095 1.0000 chr16 88450241
cg06756211 -0.2 (-0.27 ,-0.14) -6.05 0.0e+00 0.0003949 0.0021 chr1 223936799 CAPN2;CAPN2
cg06883949 -0.12 (-0.17 ,-0.08) -6.47 6.0e-07 0.0122154 0.2443 chr4 1795240 FGFR3;FGFR3;FGFR3
cg08072480 -0.14 (-0.19 ,-0.08) -6.61 1.8e-06 0.0279544 0.7217 chr11 65292666 SCYL1;SCYL1
cg10088075 -0.11 (-0.16 ,-0.07) -6.21 3.3e-06 0.0417784 1.0000 chr16 30407103 ZNF48;ZNF48
cg11480534 0.4 (0.24 ,0.55) 5.84 9.0e-07 0.0162120 0.3567 chr11 62255850 AHNAK
cg11521780 -0.14 (-0.18 ,-0.09) -5.77 0.0e+00 0.0014335 0.0115 chr12 53693949 C12orf10
cg11755803 0.41 (0.25 ,0.57) 5.79 1.4e-06 0.0237384 0.5460 chr12 129000542 TMEM132C
cg12700904 -0.11 (-0.15 ,-0.06) -5.94 1.8e-06 0.0279544 0.7268 chr3 13590720 FBLN2;FBLN2
cg12828656 -0.15 (-0.2 ,-0.11) -0.50 0.0e+00 0.0001814 0.0007 chr5 132577108 FSTL4
cg13834844 -0.15 (-0.22 ,-0.09) -5.13 1.8e-06 0.0279544 0.6946 chr10 102415320
cg13848566 -0.17 (-0.23 ,-0.11) -6.36 2.0e-07 0.0037872 0.0606 chr9 89561175 GAS1
cg14139125 -0.11 (-0.15 ,-0.06) -5.83 3.2e-06 0.0417784 1.0000 chr6 170893945 PDCD2;PDCD2
cg14149680 -0.29 (-0.38 ,-0.2) -6.35 0.0e+00 0.0001169 0.0004 chr11 2187632 TH;TH;TH
cg16560774 -0.17 (-0.23 ,-0.11) -6.46 0.0e+00 0.0017155 0.0154 chr17 79373381 BAHCC1
cg19407717 0.49 (0.35 ,0.64) 4.03 0.0e+00 0.0000387 0.0001 chr2 1544120 TPO;TPO;TPO;TPO
cg19511862 -0.1 (-0.14 ,-0.07) -6.26 4.0e-07 0.0094291 0.1697 chr12 125478458 BRI3BP
cg19641404 -0.11 (-0.16 ,-0.07) -5.87 2.4e-06 0.0340684 0.9539 chr2 232826272 DIS3L2
cg20414082 0.26 (0.16 ,0.36) 3.20 5.0e-07 0.0103493 0.1966 chr1 203002593
cg20504533 -0.22 (-0.28 ,-0.16) -5.85 0.0e+00 0.0000387 0.0001 chr17 15848253 ADORA2B;ADORA2B
cg22563312 -0.17 (-0.23 ,-0.11) -6.27 1.0e-07 0.0027236 0.0381 chr5 179334739 TBC1D9B;TBC1D9B
cg22702772 -0.15 (-0.2 ,-0.1) -6.69 1.0e-07 0.0024926 0.0308 chr3 48699012 CELSR3
cg24196240 0.42 (0.27 ,0.57) 5.27 1.0e-07 0.0031208 0.0468 chr21 36096009 NCRNA00160
cg24948962 -0.22 (-0.29 ,-0.14) -5.44 1.0e-07 0.0020477 0.0205 chr18 2906032 EMILIN2
cg25152909 0.44 (0.28 ,0.59) 6.08 1.0e-07 0.0024926 0.0324 chr5 172566090 C5orf41
cg25466588 -0.09 (-0.13 ,-0.06) -5.90 2.8e-06 0.0375151 1.0000 chr3 23958904 NKIRAS1;RPL15

DMRs

chr start end p length fdr sidak nprobe
1 161008461 161008977 0.00e+00 516 0.00e+00 0.0000000 8
19 21657528 21658001 0.00e+00 473 0.00e+00 0.0000000 5
19 10736005 10736117 0.00e+00 112 0.00e+00 0.0000052 5
20 5485244 5485511 0.00e+00 267 0.00e+00 0.0000026 6
4 79971176 79971432 0.00e+00 256 0.00e+00 0.0000055 4
20 35169593 35169886 0.00e+00 293 0.00e+00 0.0000054 5
1 9099280 9099462 1.00e-07 182 1.00e-07 0.0001508 3
10 45406680 45406847 1.00e-07 167 2.00e-07 0.0003012 3
3 39543966 39544192 2.90e-06 226 3.90e-06 0.0050930 2
15 91473090 91473365 7.70e-06 275 8.70e-06 0.0110277 4
19 12444612 12444741 8.00e-06 129 8.70e-06 0.0240202 5
5 70883064 70883087 2.07e-05 23 2.07e-05 0.2984923 3

Pb

DMP_Pb = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Pb_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  13157 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  17915 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.9851719 
 
# Number of DMRs identified:   8 

# rm(DMP_Pb); gc()

DMRs

chr start end p length fdr sidak nprobe
10 135051021 135051581 0e+00 560 0e+00 0.0000000 11
22 45704901 45705265 0e+00 364 0e+00 0.0000000 7
3 130745441 130745685 0e+00 244 1e-07 0.0000532 10
22 19746155 19746368 1e-07 213 1e-07 0.0000952 3
14 104690039 104690244 1e-07 205 1e-07 0.0001426 5
5 23507449 23507656 1e-07 207 1e-07 0.0001951 5
7 155283139 155283424 1e-07 285 1e-07 0.0001464 3
6 2891972 2892152 1e-07 180 1e-07 0.0002542 5
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb/Pb_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb/Pb_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb/Pb_log2_manhattan_DMP_adj.png")

Pb, female

DMP_Pb_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Pb_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  10571 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  12173 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.7458629 
 
# Number of identified DMR:  0

# rm(DMP_Pb_F); gc()
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_F/Pb_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_F/Pb_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_F/Pb_log2_manhattan_DMP_adj.png")

Pb, male

DMP_Pb_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Pb_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  18362 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  12544 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.8738391 

# Number of DMRs identified:   6 

# rm(DMP_Pb_M); gc()

DMRs

chr start end p length fdr sidak nprobe
6 33084548 33084985 0.0000000 437 0.0000000 0.0000000 12
1 68512649 68513063 0.0000000 414 0.0000000 0.0000008 7
6 31148331 31148748 0.0000000 417 0.0000000 0.0000009 14
22 45704987 45705265 0.0000000 278 0.0000001 0.0000607 5
22 19751653 19751899 0.0000001 246 0.0000001 0.0001654 3
19 55973098 55973234 0.0002477 136 0.0002477 0.5125157 3
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_M/Pb_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_M/Pb_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Pb_M/Pb_log2_manhattan_DMP_adj.png")

Se

DMP_Se = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Se_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  17270 
# Unadjusted, FDR<0.05:  1 
# Unadjusted, pBonf<0.05:  1 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  19895 
# Adjusted, FDR<0.05:  4 
# Adjusted, pBonf<0.05:  2 
# Adjusted, lambda:  0.9687492 

# Number of DMRs identified:   3 

# rm(DMP_Se); gc()

FDR-significant DMPs

logFC_CI AveExpr P.Value adj.P.Val adj.P.Val.bonf chr pos gene
cg08760128 0.21 (0.13 ,0.28) 6.73 2e-07 0.0327152 0.0981 chr16 4723507 MGRN1;MGRN1;MGRN1;MGRN1
cg10145926 0.55 (0.35 ,0.75) 5.31 1e-07 0.0203812 0.0408 chr14 95875792 C14orf139
cg13434714 -0.42 (-0.56 ,-0.28) -5.77 0e+00 0.0070511 0.0071 chr12 6936787 LEPREL2
cg26708724 0.59 (0.36 ,0.81) 6.73 5e-07 0.0491345 0.1965 chr4 187509785 FAT1

DMRs

chr start end p length fdr sidak nprobe
19 50194119 50194252 0 133 0 1.26e-05 5
17 47091977 47092178 0 201 0 9.00e-06 4
6 49681177 49681391 0 214 0 6.89e-05 7
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se/Se_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se/Se_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se/Se_log2_manhattan_DMP_adj.png")

Se, female

DMP_Se_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Se_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_F')

# Unadjusted, N =  158 
# Unadjusted, p<0.05:  26254 
# Unadjusted, FDR<0.05:  9 
# Unadjusted, pBonf<0.05:  2 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  15227 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.9131987 
 
# Number of DMRs identified:   5 

# rm(DMP_Se_F); gc()

DMRs

chr start end p length fdr sidak nprobe
10 38146245 38146671 0.0e+00 426 0.0e+00 0.0000001 9
6 49681177 49681391 0.0e+00 214 0.0e+00 0.0000003 7
10 38299241 38299574 0.0e+00 333 0.0e+00 0.0000053 9
1 236686563 236686804 0.0e+00 241 0.0e+00 0.0000613 4
6 42928055 42928200 7.9e-06 145 7.9e-06 0.0213843 5
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_F/Se_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_F/Se_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_F/Se_log2_manhattan_DMP_adj.png")

Se, male

DMP_Se_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Se_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  15593 
# Unadjusted, FDR<0.05:  42 
# Unadjusted, pBonf<0.05:  12 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  14283 
# Adjusted, FDR<0.05:  28 
# Adjusted, pBonf<0.05:  7 
# Adjusted, lambda:  0.8126609 
 
# Number of DMRs identified:   3 

# rm(DMP_Se_M); gc()

FDR-significant DMPs

logFC_CI AveExpr P.Value adj.P.Val adj.P.Val.bonf chr pos gene
cg00908120 0.6 (0.37 ,0.83) 6.29 1.1e-06 0.0298488 0.4477 chr16 72872925 ZFHX3;ZFHX3
cg01007589 0.79 (0.49 ,1.1) 4.79 7.0e-07 0.0210168 0.2732 chr19 49894178 CCDC155
cg01588060 -0.28 (-0.39 ,-0.18) -5.90 5.0e-07 0.0172784 0.1867 chr6 2245749 GMDS;GMDS
cg04692924 -0.6 (-0.81 ,-0.39) -6.58 1.0e-07 0.0053838 0.0323 chr1 161720042 DUSP12
cg05051957 -0.66 (-0.87 ,-0.44) -5.61 0.0e+00 0.0009331 0.0037 chr8 141522459 CHRAC1;CHRAC1
cg06723863 -0.35 (-0.47 ,-0.22) -5.99 1.0e-07 0.0055617 0.0389 chr16 68270129 ESRP2;ESRP2
cg07380021 -0.51 (-0.72 ,-0.3) -5.43 3.0e-06 0.0474750 1.0000 chr1 206755252 RASSF5;RASSF5;RASSF5
cg07599133 -0.34 (-0.47 ,-0.2) -5.96 1.8e-06 0.0428804 0.7290 chr19 35068628 LOC643719
cg08459368 0.52 (0.31 ,0.73) 2.70 2.7e-06 0.0474750 1.0000 chr11 61974948 SCGB2A1
cg08760128 0.28 (0.17 ,0.39) 6.73 1.8e-06 0.0428804 0.7131 chr16 4723507 MGRN1;MGRN1;MGRN1;MGRN1
cg10266648 0.84 (0.5 ,1.19) 5.98 3.0e-06 0.0474750 1.0000 chr2 106560529
cg11443888 0.28 (0.17 ,0.39) 2.36 2.3e-06 0.0434950 0.9134 chr6 44244590 TMEM151B
cg11608893 0.85 (0.56 ,1.14) 6.08 0.0e+00 0.0022825 0.0114 chr6 32059542 TNXB
cg12243007 0.44 (0.27 ,0.61) -0.77 1.1e-06 0.0298488 0.4290 chr17 184018 RPH3AL
cg12897502 -0.83 (-1.15 ,-0.52) 6.10 6.0e-07 0.0193412 0.2321 chr8 67425316 C8orf46
cg13434714 -0.63 (-0.8 ,-0.45) -5.78 0.0e+00 0.0000222 0.0000 chr12 6936787 LEPREL2
cg16656826 0.29 (0.17 ,0.4) 0.14 2.2e-06 0.0434950 0.8735 chr5 159343871 ADRA1B;ADRA1B
cg17515932 0.79 (0.47 ,1.12) 4.46 3.2e-06 0.0474750 1.0000 chr7 156190074
cg18377660 0.69 (0.43 ,0.95) 5.65 5.0e-07 0.0172784 0.1901 chr1 57535755 DAB1
cg19005275 0.59 (0.38 ,0.81) 4.29 3.0e-07 0.0111028 0.0999 chr12 113588263 CCDC42B
cg21373263 0.84 (0.57 ,1.11) 3.29 0.0e+00 0.0009331 0.0031 chr10 126751982 CTBP2;CTBP2
cg21864868 0.58 (0.34 ,0.81) 4.22 3.4e-06 0.0474955 1.0000 chr17 46673002 LOC404266;LOC404266;LOC404266;LOC404266;LOC404266
cg22286640 -0.73 (-1.03 ,-0.44) -4.65 2.2e-06 0.0434950 0.8497 chr8 67026828
cg23994888 -0.52 (-0.73 ,-0.31) -5.91 2.3e-06 0.0434950 0.9045 chr1 6052642 NPHP4
cg25067702 -0.63 (-0.86 ,-0.4) -6.40 2.0e-07 0.0079009 0.0632 chr17 70723227 SLC39A11;SLC39A11
cg25469351 1.29 (0.76 ,1.82) 5.96 3.1e-06 0.0474750 1.0000 chr7 6191921 USP42
cg26342676 0.61 (0.36 ,0.86) 4.56 3.0e-06 0.0474750 1.0000 chr14 37639757 SLC25A21;SLC25A21;LOC100129794
cg26708724 1.01 (0.73 ,1.3) 6.72 0.0e+00 0.0000140 0.0000 chr4 187509785 FAT1

DMRs

chr start end p length fdr sidak nprobe
17 70723226 70723386 0e+00 160 0e+00 0.0000001 2
4 24796918 24797176 0e+00 258 0e+00 0.0000151 6
10 121578383 121578639 2e-07 256 2e-07 0.0002571 3
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_M/Se_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_M/Se_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Se_M/Se_log2_manhattan_DMP_adj.png")

Zn

DMP_Zn = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal, var = 'Zn_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn')

# Unadjusted, N =  333 
# Unadjusted, p<0.05:  12854 
# Unadjusted, FDR<0.05:  1 
# Unadjusted, pBonf<0.05:  1 
 
# Adjusted, N =  333 
# Adjusted, p<0.05:  23218 
# Adjusted, FDR<0.05:  13 
# Adjusted, pBonf<0.05:  3 
# Adjusted, lambda:  1.097804 

# Number of DMRs identified:   11 

# rm(DMP_Zn); gc()

FDR-significant DMPs

logFC_CI AveExpr P.Value adj.P.Val adj.P.Val.bonf chr pos gene
cg00082497 -0.28 (-0.38 ,-0.18) -5.32 1.0e-07 0.0129186 0.0269 chr1 32802133 MARCKSL1
cg00908120 0.49 (0.3 ,0.67) 6.26 4.0e-07 0.0197441 0.1382 chr16 72872925 ZFHX3;ZFHX3
cg04015129 0.65 (0.4 ,0.91) 4.28 8.0e-07 0.0273868 0.3108 chr10 1058036 GTPBP4
cg05573434 0.42 (0.26 ,0.57) -3.15 3.0e-07 0.0175293 0.1052 chr4 7648540 SORCS2
cg06723863 -0.25 (-0.35 ,-0.15) -5.98 1.6e-06 0.0476390 0.6193 chr16 68270129 ESRP2;ESRP2
cg08459368 0.59 (0.38 ,0.81) 2.65 1.0e-07 0.0129186 0.0388 chr11 61974948 SCGB2A1
cg10653573 0.82 (0.5 ,1.13) 5.43 8.0e-07 0.0273868 0.3279 chr8 141347297 TRAPPC9;TRAPPC9
cg13434714 -0.49 (-0.64 ,-0.33) -5.77 0.0e+00 0.0012795 0.0013 chr12 6936787 LEPREL2
cg15528091 -0.31 (-0.43 ,-0.19) -6.36 7.0e-07 0.0273868 0.2933 chr19 18119069 ARRDC2;ARRDC2;ARRDC2
cg16496814 0.21 (0.13 ,0.3) 5.21 6.0e-07 0.0273868 0.2425 chr11 9778721
cg19011752 0.25 (0.15 ,0.34) -2.54 8.0e-07 0.0273868 0.3286 chr21 45772638 TRPM2
cg23477849 0.26 (0.16 ,0.35) 4.88 2.0e-07 0.0156531 0.0783 chr19 5698492 LONP1
cg25954729 -0.21 (-0.29 ,-0.14) -6.34 2.0e-07 0.0156531 0.0704 chr11 66610784 RCE1;C11orf80;RCE1

DMRs

chr start end p length fdr sidak nprobe
12 54070516 54070610 0.0000000 94 0.0000000 0.0000047 5
19 18118799 18119069 0.0000000 270 0.0000000 0.0000090 3
10 124638975 124639260 0.0000000 285 0.0000001 0.0000227 12
4 7648539 7648627 0.0000001 88 0.0000002 0.0002692 2
6 41168800 41169049 0.0000001 249 0.0000002 0.0001710 6
17 79503641 79503877 0.0000001 236 0.0000002 0.0002055 4
8 41655672 41655894 0.0000001 222 0.0000002 0.0002427 4
6 32064145 32064258 0.0000002 113 0.0000003 0.0007474 10
22 45704987 45705042 0.0000002 55 0.0000003 0.0016449 4
20 25129506 25129562 0.0000021 56 0.0000023 0.0149234 5
20 35169593 35169609 0.0095658 16 0.0095658 1.0000000 2
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn/Zn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn/Zn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn/Zn_log2_manhattan_DMP_adj.png")

Zn, female

DMP_Zn_F = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_F, var = 'Zn_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_F')

# # Unadjusted, N =  158 
# Unadjusted, p<0.05:  12830 
# Unadjusted, FDR<0.05:  0 
# Unadjusted, pBonf<0.05:  0 
 
# Adjusted, N =  158 
# Adjusted, p<0.05:  17143 
# Adjusted, FDR<0.05:  0 
# Adjusted, pBonf<0.05:  0 
# Adjusted, lambda:  0.9412223 
 
# Number of DMRs identified:   3 

# rm(DMP_Zn_F); gc()

DMRs

chr start end p length fdr sidak nprobe
11 73357018 73357396 0.0e+00 378 0.0e+00 0.0000000 8
1 120174148 120174361 9.0e-07 213 1.4e-06 0.0017026 2
10 124638975 124639012 3.2e-06 37 3.2e-06 0.0336353 4
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_F/Zn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_F/Zn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_F/Zn_log2_manhattan_DMP_adj.png")

Zn, male

DMP_Zn_M = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatAge7Metal_M, var = 'Zn_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_S_7y', 'CD4T_S_7y', 'CD8T_S_7y', 'Neu_S_7y', 'Mono_S_7y', 'NK_S_7y'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_M')

# Unadjusted, N =  175 
# Unadjusted, p<0.05:  16787 
# Unadjusted, FDR<0.05:  36 
# Unadjusted, pBonf<0.05:  8 
 
# Adjusted, N =  175 
# Adjusted, p<0.05:  14737 
# Adjusted, FDR<0.05:  36 
# Adjusted, pBonf<0.05:  3 
# Adjusted, lambda:  0.8766913 
 
# Number of DMRs identified:   16 

# rm(DMP_Zn_M); gc()

FDR-significant DMPs

logFC_CI AveExpr P.Value adj.P.Val adj.P.Val.bonf chr pos gene
cg00908120 0.8 (0.52 ,1.07) 6.29 0.0e+00 0.0063443 0.0165 chr16 72872925 ZFHX3;ZFHX3
cg01007589 0.91 (0.55 ,1.27) 4.79 2.0e-06 0.0314161 0.8041 chr19 49894178 CCDC155
cg01447660 0.42 (0.25 ,0.59) -0.92 3.7e-06 0.0417381 1.0000 chr2 69152678
cg02196294 -0.29 (-0.41 ,-0.17) -5.41 3.6e-06 0.0414185 1.0000 chr6 39197260 KCNK5
cg02490920 0.39 (0.24 ,0.55) 1.34 1.2e-06 0.0201387 0.4632 chr3 50304406 SEMA3B;SEMA3B
cg02711608 0.54 (0.35 ,0.74) -2.09 2.0e-07 0.0120512 0.0878 chr19 47287964 SLC1A5;SLC1A5;SLC1A5;SLC1A5
cg02968175 0.33 (0.2 ,0.46) 5.76 7.0e-07 0.0154847 0.2851 chr16 4690020 MGRN1;MGRN1;MGRN1;MGRN1
cg03352332 0.9 (0.57 ,1.24) 5.54 2.0e-07 0.0120512 0.0964 chr3 186360953 FETUB
cg04015129 0.86 (0.55 ,1.18) 4.27 2.0e-07 0.0120512 0.0877 chr10 1058036 GTPBP4
cg04374006 0.26 (0.16 ,0.37) -0.27 2.9e-06 0.0377171 1.0000 chr19 33556395 RHPN2
cg04406071 -0.32 (-0.45 ,-0.2) -6.07 7.0e-07 0.0154847 0.2898 chr17 59489784 C17orf82
cg04692924 -0.66 (-0.92 ,-0.41) -6.58 7.0e-07 0.0154847 0.2942 chr1 161720042 DUSP12
cg05051957 -0.66 (-0.92 ,-0.39) -5.61 2.3e-06 0.0319338 0.8941 chr8 141522459 CHRAC1;CHRAC1
cg06723863 -0.36 (-0.51 ,-0.22) -5.99 3.2e-06 0.0406663 1.0000 chr16 68270129 ESRP2;ESRP2
cg07380021 -0.65 (-0.9 ,-0.41) -5.43 5.0e-07 0.0134172 0.2147 chr1 206755252 RASSF5;RASSF5;RASSF5
cg08760128 0.36 (0.23 ,0.49) 6.73 2.0e-07 0.0120512 0.0686 chr16 4723507 MGRN1;MGRN1;MGRN1;MGRN1
cg10266648 1.04 (0.64 ,1.45) 5.98 1.2e-06 0.0201387 0.4573 chr2 106560529
cg10653573 1.42 (0.91 ,1.93) 5.37 2.0e-07 0.0120512 0.0662 chr8 141347297 TRAPPC9;TRAPPC9
cg10923018 0.31 (0.18 ,0.44) 2.73 3.5e-06 0.0414185 1.0000 chr6 31743769 C6orf27
cg11761483 -0.72 (-0.99 ,-0.45) -5.60 5.0e-07 0.0134172 0.1942 chr17 70723386 SLC39A11;SLC39A11
cg13434714 -0.84 (-1.04 ,-0.63) -5.78 0.0e+00 0.0000001 0.0000 chr12 6936787 LEPREL2
cg14230280 1.22 (0.73 ,1.71) 4.28 2.2e-06 0.0314161 0.8482 chr9 132502800 PTGES
cg16496814 0.32 (0.2 ,0.44) 5.22 4.0e-07 0.0134172 0.1415 chr11 9778721
cg16656826 0.34 (0.21 ,0.48) 0.14 2.1e-06 0.0314161 0.8405 chr5 159343871 ADRA1B;ADRA1B
cg17155018 -1.02 (-1.44 ,-0.6) 1.39 4.3e-06 0.0469139 1.0000 chr6 111953066
cg18037826 0.41 (0.25 ,0.57) 4.29 1.1e-06 0.0201387 0.4346 chr12 109273835 DAO
cg19005275 0.75 (0.49 ,1) 4.29 0.0e+00 0.0063443 0.0190 chr12 113588263 CCDC42B
cg19532212 0.76 (0.47 ,1.05) 4.42 5.0e-07 0.0134172 0.2072 chr17 56769430 TEX14;RAD51C;TEX14;RAD51C
cg21373263 0.88 (0.55 ,1.21) 3.29 5.0e-07 0.0134172 0.2067 chr10 126751982 CTBP2;CTBP2
cg22240394 1.22 (0.77 ,1.68) 6.82 4.0e-07 0.0134172 0.1707 chr3 186211630
cg22413938 -0.39 (-0.54 ,-0.23) -4.56 3.3e-06 0.0406663 1.0000 chr14 78447481
cg23477849 0.38 (0.23 ,0.53) 4.90 1.8e-06 0.0292663 0.7024 chr19 5698492 LONP1
cg23601521 0.8 (0.5 ,1.1) 4.87 5.0e-07 0.0134172 0.2111 chr2 50275179 NRXN1;NRXN1;NRXN1
cg25954729 -0.3 (-0.42 ,-0.19) -6.37 4.0e-07 0.0134172 0.1746 chr11 66610784 RCE1;C11orf80;RCE1
cg26608798 0.39 (0.23 ,0.56) 0.58 2.8e-06 0.0377171 1.0000 chr16 33853544
cg26708724 0.92 (0.56 ,1.28) 6.72 1.0e-06 0.0198743 0.3975 chr4 187509785 FAT1

DMRs

chr start end p length fdr sidak nprobe
17 70723226 70723386 0.0000000 160 0.0000000 0.0000021 2
10 121578136 121578639 0.0000000 503 0.0000000 0.0000011 4
14 78447480 78447640 0.0000000 160 0.0000000 0.0000148 3
19 50194119 50194252 0.0000000 133 0.0000000 0.0000199 5
4 24796918 24797176 0.0000000 258 0.0000000 0.0000115 6
4 186732836 186733060 0.0000000 224 0.0000000 0.0000157 7
14 76734326 76734605 0.0000000 279 0.0000000 0.0000225 5
21 45773781 45773997 0.0000000 216 0.0000000 0.0000319 2
5 135416204 135416613 0.0000000 409 0.0000000 0.0000219 9
11 63679431 63679637 0.0000001 206 0.0000002 0.0001797 2
20 62716331 62716606 0.0000001 275 0.0000002 0.0001584 4
17 78549323 78549371 0.0000001 48 0.0000002 0.0011866 3
5 1868136 1868357 0.0000003 221 0.0000004 0.0005635 4
22 45704987 45705042 0.0000017 55 0.0000019 0.0120479 4
5 176755392 176755449 0.0000125 57 0.0000133 0.0826896 2
2 88583556 88583805 0.0001149 249 0.0001149 0.1664579 3
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_M/Zn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_M/Zn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/Age7/Zn_M/Zn_log2_manhattan_DMP_adj.png")